Transcriptional and functional profiling of human embryonic stem cell-derived cardiomyocytes.
Human embryonic stem cells (hESCs) can serve as a potentially limitless source of cells that may enable regeneration of diseased tissue and organs. Here we investigate the use of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in promoting recovery from cardiac ischemia reperfusion injury in a mouse model. Using microarrays, we have described the hESC-CM transcriptome within the spectrum of changes that occur between undifferentiated hESCs and fetal heart cells. The hESC-CMs expressed cardiomyocyte genes at levels similar to those found in 20-week fetal heart cells, making this population a good source of potential replacement cells in vivo. Echocardiographic studies showed significant improvement in heart function by 8 weeks after transplantation. Finally, we demonstrate long-term engraftment of hESC-CMs by using molecular imaging to track cellular localization, survival, and proliferation in vivo. Taken together, global gene expression profiling of hESC differentiation enables a systems-based analysis of the biological processes, networks, and genes that drive hESC fate decisions, and studies such as this will serve as the foundation for future clinical applications of stem cell therapies.
Cao
Feng
F
Department of Radiology, Stanford University School of Medicine, Stanford, California, United States of America.
Wagner
Roger A
RA
Wilson
Kitchener D
KD
Xie
Xiaoyan
X
Fu
Ji-Dong
JD
Drukker
Micha
M
Lee
Andrew
A
Li
Ronald A
RA
Gambhir
Sanjiv S
SS
Weissman
Irving L
IL
Robbins
Robert C
RC
Wu
Joseph C
JC
D000818:Animals; D002454:Cell Differentiation; D004562:Electrocardiography; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000637:transplantation; D020869:Gene Expression Profiling; D006085:Graft Survival; D006801:Humans; D051379:Mice; D023421:Models, Animal; D015428:Myocardial Reperfusion Injury / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000637:transplantation; D020411:Oligonucleotide Array Sequence Analysis; D033581:Stem Cell Transplantation / Q000379:methods*; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D016896:Treatment Outcome